Stopping Aspirin Within 1 Month After Stenting for Ticagrelor Monotherapy in Acute Coronary Syndrome: The T-PASS Randomized Noninferiority Trial.

BACKGROUND: Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome. METHODS: In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point. RESULTS: Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; P<0.001 for noninferiority; P=0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; P<0.001). CONCLUSIONS: This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

BACKGROUND AND AIMS: In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. METHODS: Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. RESULTS: Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. CONCLUSIONS: In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. STUDY REGISTRATION: PROSPERO (ID: CRD42023476470).

Two novel non-coding single nucleotide variants in the DNase1 hypersensitivity site of PRDM13 causing North Carolina macular dystrophy in Korea.

Purpose: Pathogenic variants in North Carolina macular dystrophy (NCMD) have rarely been reported in the East Asian population. Herein, we reported novel variants of NCMD in 2 Korean families. Methods: The regions associated with NCMD were analyzed with genome sequencing, and variants were filtered based on the minor allele frequency (0.5%) and heterozygosity. Non-coding variants were functionally annotated using multiple computational tools. Results: We identified two rare novel variants, chr6:g.99,598,914T>C (hg38; V17) and chr6:g.99,598,926G>A (hg38; V18) upstream of PRDM13 in families A and B, respectively. In Family 1, Grade 2 NCMD and a best-corrected visual acuity of 20/25 and 20/200 in the right and left eyes, respectively, were observed. In Family B, all affected individuals had Grade 1 NCMD with characteristic confluent drusen at the fovea and a best-corrected visual acuity of 20/20 in both eyes. These two variants are 10-22 bp downstream of the reported V10 variant within the DNase1 hypersensitivity site. This site is associated with progressive bifocal chorioretinal atrophy and congenital posterior polar chorioretinal hypertrophy and lies in the putative enhancer site of PRDM13. Conclusion: We identified two novel NCMD variants in the Korean population and further validated the regulatory role of the DNase1 hypersensitivity site upstream of PRDM13.

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Weissella koreensis and Pediococcus pentosaceus bacterial ghosts induce inflammatory responses as immunostimulants.

In this study, bacterial ghosts (BGs) were generated from Weissella koreensis LKS42 (WKorGs) and Pediococcus pentosacues KA94 (PPGs) by chemically inducing lysis using substances such as hydrochloric acid (HCl), sulfuric acid (H2SO4), nitric acid (HNO3), acetic acid (CH3COOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium carbonate (Na2CO3), n-butanol, and C6H8O7. HCl-induced WKorGs and PPGs exhibited complete removal of DNA and displayed transverse membrane dissolution tunnel structures under scanning electron microscopy (SEM). Cell viability assays showed high viability of RAW 264.7 cells exposed to HCl-induced WKorGs and PPGs. Additionally, treatment with HCl-induced WKorGs and PPGs elevated mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and the anti-inflammatory cytokine IL-10 in RAW 264.7 cells. These findings suggest that HCl-induced WKorGs and PPGs have the potential to be used as inactivated bacterial immunostimulants, highlighting their promising applications in immunization and immunotherapy.

ßTrCP1 promotes SLC35F2 protein ubiquitination and inhibits cancer progression in HeLa cells.

The solute carrier family 35 F2 (SLC35F2) belongs to membrane-bound carrier proteins that are associated with multiple cancers. The main factor that determines cancer progression is the expression level of SLC35F2. Thus, identifying the E3 ligase that controls SLC35F2 protein abundance in cancer cells is critical. Here, we identified ßTrCP1 interacting with and reducing the SLC35F2 protein level. ßTrCP1 signals SLC35F2 protein ubiquitination and reduces SLC35F2 protein half-life. The mRNA expression pattern between ßTrCP1 and SLC35F2 across a panel of cancer cell lines showed a negative correlation. Additionally, the depletion of ßTrCP1 accumulated SLC35F2 protein and promoted SLC35F2-mediated cell growth, migration, invasion, and colony formation ability in HeLa cells. Overall, we demonstrate that ßTrCP1 acts as a tumor suppressor by controlling SLC35F2 protein abundance in cancer cells. The depletion of ßTrCP1 promotes SLC35F2-mediated carcinogenesis. Thus, we envision that ßTrCP1 may be a potential target for cancer therapeutics.

Impact of guideline-directed medical therapy on 5-year mortality in patients with newly diagnosed peripheral artery disease.

OBJECTIVE: Current guidelines recommend that patients with peripheral artery disease (PAD) should be treated with antithrombotic agents, renin-angiotensin-system blockers, and statins. However, the clinical impact of guideline-directed medical therapy (GDMT) on long-term mortality in patients with newly diagnosed PAD remains unclear. We aimed to investigate the prevalence of GDMT and evaluate 5-year mortality according to GDMT after PAD diagnosis. METHODS: This retrospective cohort study, using nationwide health insurance claims data in Korea, included patients newly diagnosed with PAD between 2006 and 2015. GDMT was defined as the use of all drugs, including antithrombotic agents, renin-angiotensin-system blockers, and statins, within 3 months of PAD diagnosis. The primary endpoint was all-cause mortality. RESULTS: We investigated 19,561 newly diagnosed patients with PAD without proven cardiovascular disease. Among the study population, 4378 patients (22.4%) were categorized in the GDMT and 15,183 (77.6%) in the non-GDMT groups. During the 5-year follow-up, GDMT showed a lower incidence of all-cause mortality than that of non-GDMT (2.8% vs 4.8%; adjusted hazard ratio, 0.329; 95% confidence interval, 0.257-0.421; P < .001). Even in the propensity-matched population, GDMT showed a lower mortality rate than non-GDMT (hazard ratio, 0.283; 95% confidence interval, 0.217-0.370; P < .001). As the number of guideline-recommended drugs increased, the mortality rate decreased proportionately. CONCLUSIONS: After PAD diagnosis, GDMT was associated with a lower incidence of mortality regardless of proven cardiovascular disease. This retrospective analysis showed an insufficient prevalence of GDMT among patients with PAD in real-world practice.

CLINICAL FEATURES AND PROGNOSTIC VALUE OF BACILLARY LAYER DETACHMENT IN ACUTE VOGT-KOYANAGI-HARADA DISEASE.

PURPOSE: To evaluate the characteristics of bacillary layer detachment (BALAD) in acute Vogt-Koyanagi-Harada (VKH) disease and determine its prognostic value. METHODS: Seventy patients with acute VKH disease with a minimum follow-up of 6 months were studied. The primary outcomes were clinical characteristics associated with BALAD, including features on multimodal imaging at baseline and follow-up. The secondary outcomes included best-corrected visual acuity and VKH with recurrence features. RESULTS: Of 70 eyes (36 patients), 41 (58.6%) showed BALAD. The mean baseline best-corrected visual acuity and mean best-corrected visual acuity after resolution of serous retinal detachment were significantly lower in the BALAD group than in the no-BALAD group (0.90 ± 0.49 vs. 0.35 ± 0.35 log minimum angle of resolution, P < 0.001 and 0.39 ± 0.27 vs. 0.20 ± 0.20 log minimum angle of resolution, P = 0.020). The loss of ellipsoid zone integrity at baseline, proportion of serous retinal detachment, duration of serous retinal detachment, loss of ellipsoid zone integrity at 1 month, and subfoveal choroidal thickness at baseline were significantly higher in the BALAD group ( P = 0.017, P = 0.006, P = 0.023, P = 0.002, and P = 0.046, respectively). The mean best-corrected visual acuity and subfoveal choroidal thickness did not differ between the two groups at 6 months ( P = 0.380 and P = 0.180, respectively). Bacillary layer detachment at baseline was found to be a significant prognostic factor for VKH with recurrence features ( P = 0.007). CONCLUSION: Vogt-Koyanagi-Harada with BALAD featured more severe clinical characteristics than VKH without BALAD during the acute phase. Patients with baseline BALAD require more vigilant monitoring as they are more likely to show recurrence features within the first 6 months.

Clinical features, treatment factors, and long-term outcomes of optic disc pit maculopathy.

PURPOSE: To assess the clinical features, treatment factors, and long-term visual and anatomical outcomes of optic disc pit maculopathy (ODPM) in Korean patients. METHODS: Consecutive patients diagnosed between January 2000 and September 2020 were retrospectively reviewed. The primary outcome was best-corrected visual acuity (BCVA) and anatomical changes (determined by macular thickness reduction and fluid resorption). Secondary outcomes included factors associated with poor visual outcomes (> 3-line decrease or < 20/200 vision). RESULTS: Of the 24 eyes (24 patients, mean age, 42.8 years) in this study, two peak incidence groups were noted: children younger than 14 years (six patients; mean age, 9.7 years) and middle-aged adults (18 patients; 53.8 years). There were no significant differences between groups in terms of clinical features, treatment, and outcomes (P > 0.05). The primary treatment involved immediate (7 eyes) or delayed (9) vitrectomy, laser only (2), or observation only (6). Good (50%) or partial (33%) anatomical response was noted in most cases at the final follow-up (P > 0.05). However, regression analyses showed that poor visual outcomes were associated with low preoperative BCVA (OR, 8.73; 95%CI, 1.34-56.85; P = 0.023) and delayed vitrectomy (OR, 13.00; 95%CI, 1.70-99.38; P = 0.013), while presence of intraretinal fluid in the inner and outer layers reduced the risk (OR, 0.086; 95%CI, 0.01-0.88; P = 0.039). CONCLUSION: Patients with ODPM may have two peak incidence groups with similar clinical features and treatment outcomes, supporting the idea of heterogeneous mechanisms triggering fluid accumulation. Although the primary treatment choice may not impact long-term anatomical outcomes, delayed vitrectomy may be associated with poorer visual outcomes.

Clinical features and long-term treatment outcomes in choroidal tuberculoma.

PURPOSE: To investigate the clinical features and treatment outcomes of patients with choroidal tuberculoma. METHODS: In this retrospective, observational case series, the medical records of five patients with choroidal tuberculoma who were followed up at a university hospital for at least 6 months were analyzed. RESULTS: Of five patients, one was male and four were female. The overall mean age was 38.0 ± 9.4 years (mean follow-up: 41.2 ± 33.8 months). Tuberculin skin test was performed in three patients, and it was positive in two of them. Interferon-gamma assay was performed in two patients and was positive in all two. Three patients had systemic tuberculosis involving the lung or other organs. Five patients were treated with antitubercular therapy for a period of 9.6 ± 8.6 months. Systemic corticosteroid treatment was performed in 3 patients, with a period of 3.5 ± 0.7 months. One patient with a recurrent vascularized tuberculoma was successfully treated with single intravitreal bevacizumab injection. CONCLUSION: Choroidal tuberculoma can develop without evidence of systemic tuberculosis and can recur despite antitubercular treatment. High index of suspicion is important in early detection, and management of choroidal tuberculoma. In cases of suspected choroidal tuberculoma, positive results on immunological tests would be sufficient to initiate antitubercular therapy even if radiological evidence of systemic tuberculosis is not found. Antitubercular therapy combined with systemic corticosteroids provided favorable results. Intravitreal injection of anti-vascular endothelial growth factor may be considered for highly vascularized choroidal tuberculoma.

Complications, treatments, and visual prognosis of choroidal osteomas.

PURPOSE: This study aims to report complications, treatments, and visual prognosis of choroidal osteoma. METHODS: We retrospectively reviewed electronic medical records and multimodal images of 41 patients with choroidal osteoma. RESULTS: Visually significant complications included choroidal neovascularization (CNV) in 21 (47.7%) eyes and subretinal fluid (SRF) without CNV in 14 (31.8%) eyes. The most common treatment was intravitreal anti-vascular endothelial growth factor (VEGF) injection: 13 (61.9%) eyes with CNV received an average of 6.3 injections, and 6 (42.9%) eyes with SRF but without CNV received 1.8 injections. As the first-line treatment, intravitreal anti-VEGF injection induced complete or partial remission in 93.4% of eyes with CNV and 57.1% of eyes with SRF. The probability of legally low vision estimated at 3 and at 5 years was 29.1% and 34.2%, respectively. The presence of CNV and outer retinal tubulation (ORT) was independent risk factors for vision loss (adjusted odds ratio, 8.08 and 6.94, respectively). CONCLUSIONS: The development of CNV and ORT was strong risk factors for visual impairment. Due to the frequent recurrence of complications and poor visual prognosis, regular check-ups and appropriate treatment choices are warranted.

Aberrant expression of PAX6 gene associated with classical aniridia: identification and functional characterization of novel noncoding mutations.

The PAX6 is essential for ocular morphogenesis and is known to be highly sensitive to changes in gene expression, where neither over- nor under-expression ensures normal ocular development. Two unrelated probands with classical aniridia who were previously considered "PAX6-negative", were studied by whole-genome sequencing. Through the use of multiple in silico deep learning-based algorithms, we identified two novel putative causal mutations, c.-133_-132del in the 5' untranslated region (5'-UTR) and c.-52 + 5G>A in an intron upstream of the PAX6 gene. The luciferase activity was significantly increased and VAX2 binding was disrupted with the former 5'-UTR variant compared with wild-type sequence, which resulted in a striking overexpression of PAX6. The minigene assay showed that the c.-52 + 5G>A mutation caused defective splicing, which resulted in the formation of truncated transcripts.

Safety and usefulness of a novel short track sliding balloon catheter.

OBJECTIVES: To evaluate the safety and technical utility of the short track sliding (STS) balloon catheter. BACKGROUND: An STS balloon catheter is designed to ensure a low profile at the shaft and perform distal anchoring using a single guidewire. However, its clinical practice with the STS balloon catheter has not been reported. METHODS: This prospective multi-center registry enrolled 100 patients with significant coronary artery disease who had undergone percutaneous coronary intervention using an STS balloon catheter at three hospitals in Korea from March 2019 to July 2020. Overall safety was assessed as any occurrences of device-related malfunction during the pre-dilation of the lesions. Its technical success rates of the kissing balloon technique or the distal anchoring technique using a single guidewire were also evaluated. RESULTS: Of the 118 lesions pre-dilated using the STS balloon, no significant complication was observed except for three significant coronary dissections, which were completely covered with stents. There was no incidence of balloon catheter malfunction, such as fracture, entrapment, or perforation. With 13 attempts of kissing ballooning techniques with the STS balloon with a 6F guiding catheter, all cases were successful. The distal anchoring techniques were attempted in 10 cases, the stent was successfully crossed to the target lesion in all 10 cases. CONCLUSIONS: The novel STS balloon catheter can be safely applied in routine coronary intervention with minimal complications. In addition, this catheter could be useful for performing the kissing balloon technique with a small-caliber guiding catheter and distal anchoring technique with a single guidewire.

Factors associated with ocular adverse event after immune checkpoint inhibitor treatment.

Ocular adverse events (OAEs) including vision-threatening intraocular inflammation after immune checkpoint inhibitor (ICI) treatment have been increasingly reported; however, the risk factors associated with OAEs remain elusive. Here, we determined the factors associated with OAEs after ICI treatment. We analyzed 40 consecutive patients who experienced OAEs after ICI treatments. The OAEs included anterior uveitis, chorioretinitis, papillitis, foveal interdigitation zone thickening/serous retinal detachment (IZT/SRD), retinal vascular occlusion, and strabismus and ptosis. Of 40 patients, 18 (45%) were treated with atezolizumab, 13 (33%) with pembrolizumab, 7 (18%) with nivolumab, 1 (3%) with ipilimumab/nivolumab, and the other 1 (3%) with durvalumab/tremelimumab. BRAF/MEK inhibitors were concurrently used in 19 (48%) patients. Occurrence of intraocular inflammation was significantly associated with previous ocular surgery and trauma history (P = 0.015) and pembrolizumab use (P = 0.031). Neuro-ophthalmic complications and IZT/SRD were associated with brain metastasis (P = 0.005) and treatment with BRAF/MEK inhibitor (P < 0.001), respectively. In extensive literature review for clinical cases, we identified seven cases with intraocular inflammation, which were not observed with ipilimumab treatment, that occurred after a change of the drug to pembrolizumab. Collectively, these findings provide better understandings of OAEs after ICI treatment.

Copy number variations and multiallelic variants in Korean patients with Leber congenital amaurosis.

Purpose: We comprehensively evaluated the mutational spectrum of Leber congenital amaurosis (LCA) and investigated the molecular diagnostic rate and genotype-phenotype correlation in a Korean cohort. Methods: This single-center retrospective case series included 50 Korean patients with LCA between June 2015 and March 2019. Molecular analysis was conducted using targeted panel-based next-generation sequencing, including deep intronic and regulatory variants or whole exome sequencing. The molecular diagnosis was made based on the inheritance pattern, zygosity, and pathogenicity. Results: Among the 50 patients, 27 patients (54%) were male, and 11 (22%) showed systemic features. Genetic variants highly likely to be causative were identified in 78% (39/50) of cases and segregated into families. We detected two pathogenic or likely pathogenic variants in a gene linked to a recessive trait without segregation analysis in three cases (6.0%). GUCY2D (20%), NMNAT1 (18%), and CEP290 (16%) were the most frequently mutated genes in Korean LCA. Copy number variations were found in three patients, which accounted for 6% of LCA cases. A possible dual molecular diagnosis (Senior-Løken syndrome along with Leigh syndrome, and Joubert syndrome with transposition of the great arteries) was made in two patients (4%). Three of 50 patients were medically or surgically actionable: one patient for RPE65 gene therapy and two patients with WDR19 Senior-Løken syndrome for early preparation for kidney and liver transplantations. Conclusions: This study demonstrated that approximately 4% of patients may have dual molecular diagnoses, and 6% were surgically or medically actionable in LCA. Therefore, accurate molecular diagnosis and careful interpretation of next-generation sequencing results can be of great help in patients with LCA.

DRUSEN SUBTYPES AND CHOROIDAL CHARACTERISTICS IN ASIAN EYES WITH TYPICAL NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the prevalence of pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with different neovascular age-related macular degeneration (nAMD) subtypes, determine the relationship between each drusen type and the choroidal thickness, and analyze the distinct features of each nAMD subtype according to the drusen type. METHODS: Medical records involving 454 eyes from 454 patients with nAMD were retrospectively reviewed. The prevalence of each drusen type and the choroidal thickness and choroidal characteristics were evaluated according to the nAMD subtype. RESULTS: Pachydrusen were prevalent in the typical nAMD (40.4%) and polypoidal choroidal vasculopathy (47.8%) groups and were not detected in the retinal angiomatous proliferation group. No significant drusen were detected in 24.3% of typical nAMD, 43.3% of polypoidal choroidal vasculopathy, and 0% of retinal angiomatous proliferation groups. Regardless of the nAMD subtype, pachydrusen, soft drusen, and subretinal drusenoid deposits were associated with a thick, moderately thick, and thin choroid, respectively. For eyes with typical nAMD, the prevalence of choroidal vascular hyperpermeability and extrafoveal neovascularization was significantly higher in the pachydrusen group than in the other groups. By contrast, the prevalence of Type 2 neovascularization was significantly lower in the pachydrusen group than in the subretinal drusenoid deposit group (P < 0.001 for all). CONCLUSION: The prevalence of various drusen differed according to the nAMD subtypes, and each drusen type was strongly associated with the choroidal thickness. Typical nAMD showed distinct features according to the accompanying drusen type.

In-hospital outcome differences between transradial and transfemoral coronary approaches: Data from the Korean percutaneous coronary intervention registry.

OBJECTIVES: We aimed to investigate specific subgroups in which the benefit of transradial coronary interventions (TRIs) would be enhanced. BACKGROUND: The advantage of TRIs over transfemoral coronary interventions (TFIs) might differ according to a given clinical condition, urgency of the procedure, and operator volume pattern. METHODS: Using a cohort from the 2014 Korean Percutaneous Coronary Intervention Registry, in-hospital outcomes of the TRI group (n = 22,993) were matched to those of the TFI group (n = 15,581). After propensity score matching, the composite endpoints between the groups and subgroups for all-cause death, nonfatal myocardial infarctions (MIs), or transfusions were analyzed. RESULTS: The composite endpoints occurred less frequently in the TRI group than the TFI group [2.1% vs. 5.5%, OR 0.63, 95% CI 0.55-0.72]. The TRI group had a lower rate of death (OR 0.44, 95% CI 0.33-0.60) and nonfatal MI (OR 0.66, 95% CI 0.54-0.81) than the TFI group. The TRI group required fewer transfusions than the TFI group (OR 0.72, 95% CI 0.59-0.88). TRI benefits were consistent across subgroups except patients with chronic kidney disease and those treated in low tertile PCI volume centers. The favorable outcome of TRI was greater in the elderly (≥75 years), patients with ST-elevation MI, those who underwent emergent PCI, and those treated in high tertile PCI volume hospitals (P for the interaction <0.001 for all). CONCLUSIONS: Compared to TFI, TRI had favorable composite in-hospital outcomes. TRI benefits were pronounced in high-risk clinical settings and in high PCI volume centers.

Co-treatment with interferon-γ and 1-methyl tryptophan ameliorates cardiac fibrosis through cardiac myofibroblasts apoptosis.

Cardiac remodeling characterized by cardiac fibrosis is a pathologic process occurring after acute myocardial infarction. Fibrosis can be ameliorated by interferon-gamma (IFN-γ), which is a soluble cytokine showing various effects such as anti-fibrosis, apoptosis, anti-proliferation, immunomodulation, and anti-viral activities. However, the role of IFN-γ in cardiac myofibroblasts is not well established. Therefore, we investigated the anti-fibrotic effects of IFN-γ in human cardiac myofibroblasts (hCMs) in vitro and whether indoleamine 2,3-dioxygenase (IDO), induced by IFN-γ and resulting in cell cycle arrest, plays an important role in regulating the biological activity of hCMs. After IFN-γ treatment, cell signaling pathways and DNA contents were analyzed to assess the biological activity of IFN-γ in hCMs. In addition, an IDO inhibitor (1-methyl tryptophan; 1-MT) was used to assess whether IDO plays a key role in regulating hCMs. IFN-γ significantly inhibited hCM proliferation, and IFN-γ-induced IDO expression caused cell cycle arrest in G0/G1 through tryptophan depletion. Moreover, IFN-γ treatment gradually suppressed the expression of α-smooth muscle actin. When IDO activity was inhibited by 1-MT, marked apoptosis was observed in hCMs through the induction of interferon regulatory factor, Fas, and Fas ligand. Our results suggest that IFN-γ plays key roles in anti-proliferative and anti-fibrotic activities in hCMs and further induces apoptosis via IDO inhibition. In conclusion, co-treatment with IFN-γ and 1-MT can ameliorate fibrosis in cardiac myofibroblasts through apoptosis.

PREVALENCE AND CLINICAL CHARACTERISTICS OF PACHYDRUSEN IN POLYPOIDAL CHOROIDAL VASCULOPATHY: Multimodal Image Study.

PURPOSE: To investigate the prevalence of a newly defined drusen type, pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with polypoidal choroidal vasculopathy and fellow eyes and the relationship between each drusen type and the choroidal thickness, vascular morphology, and hyperpermeability. METHODS: The 169 eyes of 90 patients with polypoidal choroidal vasculopathy were retrospectively reviewed. The prevalence of each drusen type was evaluated using color fundus photography and optical coherence tomography. The choroidal thickness and presence of pachyvessels on optical coherence tomography and choroidal vascular hyperpermeability on indocyanine green angiography were compared among the drusen groups. RESULTS: Pachydrusen, soft drusen, and subretinal drusenoid deposits were found in 49.3%, 12.3%, and 6.9% in polypoidal choroidal vasculopathy eyes. The mean subfoveal choroidal thickness of the pachydrusen, soft drusen, and subretinal drusenoid deposit groups was 403.1, 184.4, and 176.4 µm. The pachydrusen group showed significantly thicker choroid than the others. The choroidal hyperpermeability was noticed at 41.7%, 0%, and 0% and the pachyvessel was observed at 80.6%, 44.4%, and 40% in pachydrusen, soft drusen, and subretinal drusenoid deposit groups, respectively. CONCLUSION: In patients with polypoidal choroidal vasculopathy, pachydrusen was prevalent and associated with thicker choroid. Polypoidal choroidal vasculopathy with pachydrusen was highly associated with choroidal vascular hyperpremeability and pachyvessel morphology than other types of drusen.

DIFFERENTIAL DIAGNOSIS FOR VITREORETINAL LYMPHOMA WITH VITREORETINAL FINDINGS, IMMUNOGLOBULIN CLONALITY TESTS, AND INTERLEUKIN LEVELS.

PURPOSE: To analyze vitreoretinal findings, immunoglobulin clonality tests, and interleukin (IL) levels for diagnosing vitreoretinal lymphoma (VRL). METHODS: Forty-three patients who underwent diagnostic vitrectomy for suspected VRL were retrospectively reviewed. Of those patients finally diagnosed with VRL and nonlymphoma, ophthalmic evaluation and cytology results, IL-6 and IL-10 levels, and immunoglobulin heavy chain and immunoglobulin kappa light chain clonality assays were compared. RESULTS: Sub-retinal pigment epithelium infiltration and veil-pattern vitreous opacity were specific vitreoretinal findings in patients with VRL. The area under the receiver operating characteristic curve of the IL-10-to-IL-6 ratio and of IL-10 levels was 0.972 and 0.931, respectively. A combined immunoglobulin heavy chain and immunoglobulin kappa light chain assay showed increased sensitivity, whereas the determined specificity of immunoglobulin kappa light chain, at 94.12%, was much higher than the 78.95% of immunoglobulin heavy chain. Patients with VRL with atypically elevated IL-6 levels showed extensive and severe sub-retinal pigment epithelium infiltration. CONCLUSION: Newly screened immunoglobulin kappa light chain clonality assays may be useful to distinguish VRL from uveitis with high specificity. When sub-retinal pigment epithelium or retinal infiltration is severe and extensive, the IL-10-to-IL-6 ratio may not be typical and should be carefully interpreted.